Study Of White Blood Cells In The Cerebrospinal Fluid And Blood Of Patients With Relapsing Forms Of Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00469378
First received: May 2, 2007
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

This is a study to count the number of white blood cells in the cerebrospinal fluid and blood at the beginning and end of treatment with firategrast and at 4 and 12 weeks after stopping firategrast. Cerebrospinal fluid flows through and protects the brain and spinal cord. It is important to understand what happens to the number of white blood cells because they are important in preventing infections.


Condition Intervention Phase
Multiple Sclerosis
Drug: firategrast
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study of Leukocyte Counts in the Cerebrospinal Fluid and Blood of Subjects With Relapsing Forms of Multiple Sclerosis Following Treatment With Firategrast

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of leukocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of leukocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of leukocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of leukocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD4+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD4+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD4+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD4+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD8+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD8+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD8+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD8+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD19+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD19+ lymphocytes in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD19+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD19+ lymphocytes in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD3+CD16+CD56+ natural killer cells in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD3+CD16+CD56+ natural killer cells in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of CD3+CD16+CD56+ natural killer cells in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in number of CD3+CD16+CD56+ natural killer cells in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • CD4:CD8 ratio in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in CD4:CD8 ration in CSF [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • CD4:CD8 ratio in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in CD4:CD8 ratio in blood [ Time Frame: At the end of 24 weeks treatment with firategrast and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of CD34+ cells in the blood [ Time Frame: At 4 weeks after starting firategrast, at the end of 24 weeks treatment and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 76 weeks ] [ Designated as safety issue: No ]
  • The relationship between plasma concentration of firategrast and lymphocyte count in the CSF [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
  • Change in number of CD34+ cells in the blood [ Time Frame: At 4 weeks after starting firategrast, at the end of 24 weeks treatment and at 4 and 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • The relationship between plasma concentration of firategrast and lymphocyte count in the blood [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
  • The relationship between the presence of the A allele of rs887829 and bilirubin levels [ Time Frame: Through Week 36 ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: July 2007
Study Completion Date: February 2010
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: firategrast
900 (females) or 1200 (males) mg twice daily for 24 weeks
Drug: firategrast
900 (females) or 1200 (males) mg twice daily for 24 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Specific information regarding warnings, precautions, contraindications, adverse events (AEs), and other pertinent information on the investigational product that may impact subject eligibility is provided can be found in the SB-683699 Investigators Brochure [GlaxoSmithKline Document Number HM2002/00094/05].

Subjects eligible for enrollment in the study must meet all of the following criteria:

  • Written informed consent.
  • Male or female, age 18 to 65.
  • A diagnosis of a relapsing form of MS [As per McDonald, 2001; Polman, 2005], with dissemination in time and space.
  • Expanded Disability Status Scale (EDSS) score of between 0 and 6.5 inclusive.
  • Occurrence of at least one clinical attack in the previous 24 months, but not within the 4 weeks prior to Screening or prior to the Baseline Visit.
  • A minimum of two T2 lesions on brain MRI at Screening, as determined by the central MRI analysis reader.
  • A female subject is eligible to enter the study if she is:

    1. Of non-childbearing potential, i.e. a woman who:

      • has documented evidence of tubal ligation, bilateral oophorectomy or hysterectomy; or
      • is post-menopausal, defined as at least one year without menses in the absence of hormone replacement therapy. In questionable cases, menopausal status will be confirmed by estradiol and Follicle Stimulating Hormone (FSH) levels consistent with menopause according to local laboratory ranges. Estrogen-containing hormone replacement therapies (HRT) are not allowed during the study.

      OR

    2. Of childbearing potential, has a negative urine pregnancy test at Screening and Baseline, and agrees to consistent and correct use the method of contraception listed below. Subjects will use effective contraceptive methods for at least one month prior to Screening and should continue to use the same contraceptive method throughout the study until 3 days after the last dose of firategrast.

      • Progesterone-only oral contraceptives or implants (inserted at least one month prior to Screening, but not beyond the third successive year following insertion). Estrogen-containing contraceptives are not allowed during the study.
      • Intrauterine Device (IUD) (inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year).
      • Spermicide in conjunction with either a diaphragm, cervical cap or condom.
      • Male partner sterilization (vasectomy) prior to female subject's entry into the study and is the sole partner for that female subject.

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

  • Subjects receiving corticosteroids within 4 weeks of Screening for treatment of MS. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the investigator after discussion with the GSK medical monitor.
  • Use of a b-interferon product, glatiramer acetate or azathioprine within 3 months of Screening, or use of Mitoxantrone within 12 months of Screening. Subjects who have received other therapies affecting the immune system (such as intravenous immunoglobulin (IVIg), cyclophosphamide, plasmapheresis, or any other immunosuppressive or immunomodulatory treatment) in the past may be included on a case by case basis after discussion with the GSK medical monitor. None of these treatments will be allowed during this study.
  • Previous exposure to alemtuzumab, natalizumab or firategrast administration, bone marrow transplantation or whole body irradiation.
  • Subjects with a cardiac pacemaker or any other type of metal implant or with any other contraindication for MRI (including known allergy to gadolinium).
  • Use of 4-aminopyridine, rosiglitazone, pioglitazone or any drug that is an inhibitor of or a substrate (with a low therapeutic index) for Organic Anion Transporter Protein (OATP).
  • Subjects with clinically significant renal laboratory values: subjects with a calculated creatinine clearance <60ml/min (by Cockcroft and Gault) at Screening [Cockcroft, 1976].
  • Subjects with local urinalysis findings of 1) proteinuria, defined as ³1+ protein on urine dipstick or 2) renal tubular cell casts or 3) ³5 red blood cells / high power field will be excluded from the study if the result is still present on a repeat urinalysis during the Screening Phase.
  • Presence of clinically significant hepatic laboratory values: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT) > 2 times the upper limit of the reference range; total bilirubin > 1.5 the upper limit of the normal range.
  • CD4 count < 500, CD4:CD8 < 1.0, JCV viremia in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening.
  • Any findings at Screening on the MRI of the brain other than MS, except for benign findings that (in the opinion of the central MRI reading site and local site investigator) require no further evaluation or treatment and do not impact patient's neurological health (e.g. small arachnoid cysts, venous angiomas).
  • Uncontrolled or any active bacterial, viral, or fungal infection. Any previous serious infections should be discussed with the GSK medical monitor (e.g. opportunistic or atypical infections).
  • History of tuberculosis (TB) or positive chest X-ray for TB at Screening (prior chest X-ray is acceptable if performed within previous 6 months).
  • Known congenital or acquired immunodeficiency.
  • Current or history of cancer, excluding localized non-melanoma skin cancer.
  • Any abnormality on 12-lead Electrocardiogram (ECG) at Screening which is clinically significant in the opinion of the investigator.
  • Positive hepatitis B surface antigen, hepatitis C antibody or HIV tests at Screening.
  • Women who are lactating, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the course of the study.
  • Recent history or suspicion of current drug abuse (including analgesic abuse) or alcohol abuse within the last 6 months prior to Screening. Alcohol abuse is defined as an average weekly intake of greater than 21 units for men and 14 units for women or an average daily intake of greater than three units for men and two units for women. One unit is equivalent to approximately 250mL of beer or one measure of spirits or one glass of wine.
  • Use of an investigational drug for a condition other than MS within 30 days or 5 half-lives (whichever is longer) preceding Screening. Prior use of an investigational drug for MS should be discussed with the GSK medical monitor.
  • Any concurrent illness, disability or clinically significant abnormality (including laboratory tests) that may affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol.
  • Contraindications, in the opinion of the investigator, to lumbar puncture, e.g. congenital or acquired spine or CNS conditions that may render LPs unsafe, platelet count of less than 50 GI/L and/or an International Normalized Ratio (INR) of greater than or equal to 1.5 (by history), known history of clotting/bleeding disorder, needle phobia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469378

Locations
Belgium
GSK Investigational Site
Bruxelles, Belgium, 1200
GSK Investigational Site
Bruxelles, Belgium, 1070
Czech Republic
GSK Investigational Site
Olomouc, Czech Republic, 775 20
GSK Investigational Site
Praha 2, Czech Republic, 120 00
Denmark
GSK Investigational Site
Glostrup, Denmark, DK-2600
GSK Investigational Site
Koebenhavn Ø, Denmark, 2100
Norway
GSK Investigational Site
Lørenskog, Norway, 1478
Sweden
GSK Investigational Site
Göteborg, Sweden, SE-416 85
GSK Investigational Site
Stockholm, Sweden, SE-171 76
GSK Investigational Site
Umeå, Sweden, SE-901 85
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00469378     History of Changes
Other Study ID Numbers: A4M108119
Study First Received: May 2, 2007
Last Updated: July 3, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
firategrast
lymphocytes
leukocytes
SB-683699
cerebrospinal fluid
relapsing forms of multiple sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014